Accelerating the Development of an Extended-specificity Multiplex Urine Immunoassay for the Diagnosis and Serotyping of Pneumococcal Pneumonia in High Carriage and Disease Burden Settings Like Malawi
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Number of participants with serotype-specific urinary pneumococcal antigen detected
研究概览
简要总结
Background:
Pneumonia caused by the bacteria Streptococcus pneumoniae is a leading cause of death among children under five years of age, especially in sub-Saharan Africa. Accurate diagnosis remains challenging due to the need for invasive procedures to obtain samples for culture-based diagnostic tests, which are not very sensitive for detecting S.pneumoniae, particularly after antibiotic use.
Serotype-specific urinary antigen detection (ssUAD) assays are a promising, non-invasive alternative for the surveillance and diagnosis of pneumococcal disease. Importantly, they can identify different serotypes of S.pneumoniae, which is crucial for monitoring vaccine impact. However, the ability of the ssUAD to identify invasive disease due to S.pneumoniae has not been studied in children in sub-Saharan Africa, where high rates of asymptomatic carriage may affect diagnostic accuracy.
Aim:
The overall aim of this study is to evaluate the performance of the ssUAD test to detect pneumococcal carriage, and distinguish it from invasive disease, among children under five years old in Blantyre, Malawi.
Methods:
This study will test 350 existing urine samples that have already been collected from children as part of the NP Resistome study (LSTM reference 24-076), including healthy children in the community, children with pneumonia in the community, and children hospitalised with pneumonia. Participants of the NP Resistome study will be recruited from Ndirande Health Centre (NHC), Gateway Primary Care Centre (GPCC) and Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. Aliquots from each urine sample will be tested using the ssUAD in the UK, as the assay is not currently available in Malawi. Urinary detection of pneumococcal serotypes will be compared with both culture-based and metagenomic sequencing results from nasopharyngeal swab samples taken as part of the main study.
详细描述
Study type:
This is a nested case-control sub-study within the multi-site, observational NP Resistome study (COMREC reference P.10/24-1200).
Background:
Pneumococcal pneumonia is a leading cause of morbidity and mortality among children under five, especially in sub-Saharan Africa. Accurate diagnosis remains a challenge due to the need for invasive specimen collection and poor sensitivity of standard culture-based diagnostic tests, particularly after antibiotic use. Serotype-specific urinary antigen detection (ssUAD) offers a promising, non-invasive alternative for serotype surveillance and diagnosis of pneumococcal disease. Serotype-specific identification provided by ssUAD is crucial for monitoring the impact of vaccines and informing public health interventions. The ssUAD test is a Luminex-based urine antigen capture assay developed by the UK Health Security Agency (UKHSA) that targets 24 pneumococcal serotypes, with good sensitivity and specificity among adults with community-acquired pneumonia in the UK. Further investigation is required to determine its ability/utility to identify invasive disease among children, particularly in settings like sub-Saharan Africa, where high rates of asymptomatic carriage may affect diagnostic accuracy.
Broad Objective: To evaluate the performance of the ssUAD test in detecting pneumococcal carriage and distinguishing it from invasive disease among children under five years old in Blantyre, Malawi.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Months 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for healthy children in the community
- •Child aged between12-24 months.
排除标准
- •for healthy children in the community
- •Presence of any of the following symptoms: fever, cough, difficulty in breathing or fast breathing.
- •Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications.
- •Diagnosis of an immunosuppressive illness, including HIV infection.
- •Hospital admission within the past six months.
- •Inclusion criteria for children with pneumonia in the community
- •Child aged between12-24 months.
- •Presence of all of the following symptoms: fever, cough, difficulty in breathing and fast breathing.
- •Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this presentation.
- •Exclusion criteria for children with pneumonia in the community
- •Severe anaemia, with a recorded haemoglobin level < 70 grams per Litre.
- •Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications.
- •Diagnosis of an immunosuppressive illness, including HIV infection.
- •Hospital admission within the past six months.
- •Inclusion criteria for children hospitalised with pneumonia
- •Child aged between 12-24 months.
- •Presence of all of the following symptoms: fever, cough, difficulty in breathing and fast breathing.
- •Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this presentation.
- •Exclusion criteria for children hospitalised with pneumonia
- •Severe anaemia, with a recorded haemoglobin level < 70 grams per Litre.
- •Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications.
- •Diagnosis of an immunosuppressive illness, including HIV infection.
- •Hospital admission within the past six months.
- •Inclusion criteria for children re-hospitalised with pneumonia
- •Child aged between12-24 months.
- •Presence of all of the following symptoms: fever, cough, difficulty in breathing and fast breathing.
- •Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this presentation.
- •Hospital admission to ANY hospital with a lower respiratory tract infection within the past 3 months.
- •Exclusion criteria for children re-hospitalised with pneumonia
- •Severe anaemia, with a recorded haemoglobin level < 70 grams per Litre.
- •Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications.
- •Diagnosis of an immunosuppressive illness, including HIV infection.
研究组 & 干预措施
Healthy community
Healthy children living in Ndirande community, aged between 12 and 24 months at recruitment.
Community pneumonia
Children aged between 12 and 24 months who have presented to Ndirande Health Centre with a pneumonia clinical syndrome (based on the WHO definition of fever, cough, tachypnoea and dyspnoea) for which they are prescribed antibiotic therapy.
Hospital pneumonia - first admission
Children aged between 12 and 24 months who have been admitted to Queen Elizabeth Central Hospital for the first time with a pneumonia clinical syndrome (based on the WHO definition of fever, cough, tachypnoea and dyspnoea) for which they are prescribed antibiotic therapy.
Hospital pneumonia - re-admission
Children aged between 12 and 24 months who have been re-admitted to Queen Elizabeth Central Hospital with a pneumonia clinical syndrome (based on the WHO definition of fever, cough, tachypnoea and dyspnoea) for which they are prescribed antibiotic therapy, within 3 months of a previous hospitalisation with pneumonia.
结局指标
主要结局
Number of participants with serotype-specific urinary pneumococcal antigen detected
时间窗: At the time of recruitment/participant enrolment.
Number of participants with serotype-specific pneumococcal antigen detected in urine samples taken at recruitment, using an extended-specificity multiplex urine immunoassay.
Serotype specific urinary pneumococcal antigen detection
时间窗: At the time of recruitment/participant enrolment.
Serotype-specific urinary pneumococcal antigen detection in urine samples taken at recruitment, using an extended-specificity multiplex urine immunoassay.
次要结局
- Number of participants with nasopharyngeal carriage of Streptococcus pneumoniae (detected based on culture)(At time of recruitment/enrolment.)
- Nasopharyngeal pneumococcal carriage(At time of recruitment/enrolment.)